Patients can have increases or decreases in the percentage of certain chemicals or other elements, either throughout the body or in certain organs or other body parts, as a direct or indirect result of certain diseases. For example, osteoporosis, a widespread condition afflicting 15 to 20 million individuals in the United States alone, results from loss of mineral content of bone. As the bone loses mass and structural strength, the patient becomes susceptible to fractures. The principal mineral lost when osteoporosis occurs is calcium. Therefore, detection of calcium loss in bone should serve as a reliable indicator of osteoporosis.
However, current techniques for in vivo measurement generally measure bone mineral density rather than the fraction of body calcium in all or a portion of a patient's body. These technique include radiography of portions of the spinal column which, while readily available, is a crude measure, a loss of approximately 30% being necessary for osteoporosis to become evident by this technique. Other more sensitive techniques include radiogrammetry, photodensitometry, whole and partial body neutron activation, single and dual photon absorptometry, single and dual energy computed tomography and Compton scattering. Such measurements are made on part of the spine, the whole spine, the wrist, the hand or the heel, according to the technique used. While these techniques for measuring bone mineral density can be useful in the detection of, for example, osteoporosis, they also have a number of drawbacks.
One potential problem is that most of these techniques depend on the fact that bone absorbs certain radiations at a different rate than other portions of the body. However, for the current techniques, there are other portions of the body which absorb certain radiation at a rate which is not radically different from that of bone, resulting in potential errors in readings. For example, the percentage loss indicated by such techniques may be less than the actual percentage loss in bone density because the readings are picking up parts of the body, in addition to just bone.
A second potential problem is that the x ray or other radiation doses for all of the techniques are relatively high. For this reason, these techniques are generally performed on only a small portion of the body, an assumption being made that bone loss is uniform throughout the body. There is some controversy in the medical profession as to whether this is a valid assumption for all patients.
The relatively high doses also prevent the techniques from being used for early screening of patients, the techniques generally being used only for patients in high risk groups or where other indications exist that osteoporosis might be present.
The situation in detecting other elements in the body is even less advanced than that for calcium. For example, nitrogen is a major constituent (approximately 16%) of body protein, but is fractionally smaller in other body compartments. It may thus be possible to detect the mass of protein in a patient's body non-invasively from total body nitrogen measurements. Such total body nitrogen analysis can be used to monitor changes in body composition of cancer patients and assess the efficacy of various therapeutic regimens. Similarly, body composition measurements can be utilized to provide an understanding of AIDS-related malnutrition and to assess various nutritional therapies. Such techniques would also be useful in the diagnosis and treatment of other diseases which result in debilitation of the patient, and in particular in the debilitation of all or selected muscles of the patient or in nutritional debilitation.
Present non invasive methods for detecting a single element such as nitrogen in the body, such as those based on prompt-gamma neutron activation, monitor only the total body content of these elements, rather than their distribution throughout the body. Thus, serial measurements to monitor changes in total-body nitrogen do not reveal whether some fat-free tissue or particular organs gain or lose more protein than others. This may be undesirable since monitoring in vivo changes in the nitrogen content of individual organs or other body parts might lead to a better understanding of the mechanism of protein gain and loss and might be useful in diagnosing certain disorders, or the situs of certain disorders such as polio. However, present methods do not have the ability to determine element distributions because the required dosage would be to high.
This points up a second major disadvantage of existing techniques in that they require relatively high radiation doses, for example 27 mrem for a 1% accuracy in whole body measurement of nitrogen. This dosage is high enough so that measurements cannot be taken at frequent intervals to assess the effectiveness of a therapeutic regimen and screening tests would not be performed, tests only being performed when it is clear that a problem exists. Even when performed at infrequent intervals, tests performed at that radiation level can be potentially hazardous and would not normally be performed on, for example, young children or pregnant woman. As indicated above the radiation dosage required absolutely precludes the use of such techniques for localized nitrogen content assessment.
Other disadvantages of present chemical element detection techniques are the requirement of a radioactive source and the large size of the measurement system. Present use of radioactive plutonium as a source presents a security problem and requires extensive safeguards. It also presents a disposal problem for radioactive waste. Since a radioactive source cannot be turned off when not in use, heavy shielding must be provided which contributes to the size, weight and cost of such systems. Because of this and other factors, the large size of such measuring systems makes installation in a hospital unmanageable. As a result, clinical examinations using such equipment are currently limited to elaborate off-site facilities, rather than more appropriate hospital or health-care facilities located in or near population centers. The need to send patients to off site facilities, facilities which are frequently at some distance from the hospital where the patient is located, further increase the cost and inconvenience of using such equipment. As a result, the use of such equipment is not feasible for large classes of patients, including critically ill patients who are frequently the ones most in need of such testing.
A need therefore exists for an improved method and apparatus for performing non-invasive, and preferably in vivo, detection, and measurement of a single chemical or other element in a patient's body. Such technique should result in minimal radiation exposure so that tests may be utilized for screening, may be performed at frequent intervals to assess the efficacy of nutritional or other treatment regimen and may, in some instances, be utilized with young children, pregnant women and other potentially high risk classes of patients. Low dosage would also permit measurements to be made on selected body areas, in addition to total body measurements. The technique should also permit the body content of selected elements to be measured directly and should provide accurate indications of the content of such chemical element. Finally, the equipment should not require the use of a radioactive source, and it should be possible to fabricate the equipment for practicing the technique so that such equipment is small and inexpensive enough to be utilized at hospitals or other health care facilities where a need for such equipment exists.